Molecular and Cellular Biology, May 2001, p. 3071-3082, Vol. 21, No. 9
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.9.3071-3082.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

andDepartment of Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032
Received 24 March 2000/Returned for modification 5 June 2000/Accepted 5 February 2001
Expression of the CD4 gene is tightly controlled throughout
thymopoiesis. The downregulation of CD4 gene expression in
CD4
CD8
and CD4
CD8+ T lymphocytes is controlled by a transcriptional
silencer located in the first intron of the CD4 locus. Here, we
determine that the c-Myb transcription factor binds to a functional
site in the CD4 silencer. As c-Myb is also required for CD4 promoter
function, these data indicate that depending on the context, c-Myb
plays both positive and negative roles in the control of CD4 gene
expression. Interestingly, a second CD4 silencer-binding factor, HES-1,
binds to c-Myb in vivo and induces it to become a transcriptional
repressor. We propose that the recruitment of HES-1 and c-Myb to the
silencer leads to the formation of a multifactor complex that induces
silencer function and repression of CD4 gene expression.
Present address: Department of Pathology, Washington University
School of Medicine, St. Louis, MO 63110.
Present address: Experimental Immunology Branch, National Cancer
Institute, Bethesda, MD 20892-1360.
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